Cancer initiation and progression are likely caused by the dysregulation of biological pathways. Gene set analysis (GSA) could improve the signal-to-noise ratio and identify potential biological insights on the gene set level. However, platforms exploring cancer multi-omics data using GSA methods are lacking. In this study, we upgraded our GSCALite to GSCA (gene set cancer analysis, http://bioinfo.life.hust.edu.cn/GSCA) for cancer GSA at genomic, pharmacogenomic and immunogenomic levels. In this improved GSCA, we integrated expression, mutation, drug sensitivity and clinical data from four public data sources for 33 cancer types. We introduced useful features to GSCA, including associations between immune infiltration with gene expression and genomic variations, and associations between gene set expression/mutation and clinical outcomes. GSCA has four main functional modules for cancer GSA to explore, analyze and visualize expression, genomic variations, tumor immune infiltration, drug sensitivity and their associations with clinical outcomes. We used case studies of three gene sets: (i) seven cell cycle genes, (ii) tumor suppressor genes of PI3K pathway and (iii) oncogenes of PI3K pathway to prove the advantage of GSCA over single gene analysis. We found novel associations of gene set expression and mutation with clinical outcomes in different cancer types on gene set level, while on single gene analysis level, they are not significant associations. In conclusion, GSCA is a user-friendly web server and a useful resource for conducting hypothesis tests by using GSA methods at genomic, pharmacogenomic and immunogenomic levels.

Recent studies emphasize the significance of copper dyshomeostasis in neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, thereby highlighting the role of copper in neurotoxicity. Cuproptosis, a novel mechanism of copper-dependent cell death, remains underexplored, particularly concerning environmental pollutants like polystyrene nanoplastics (PS-NPs). While PS-NPs are recognized for inducing neurotoxicity through various forms of cell death, including apoptosis and ferroptosis, their potential to trigger neuronal cuproptosis has not yet been investigated. This study aims to determine whether exposure to PS-NPs induces neurotoxicity via cuproptosis and to explore the preliminary molecular mechanisms involved, thereby addressing this significant knowledge gap. Seven-week-old male C57BL/6 mice were exposed to PS-NPs at dose of 12.5 mg/kg, and were co-treated with the antioxidant N-acetylcysteine (NAC). Complementary in vitro experiments were conducted using SH-SY5Y neuronal cells exposed to PS-NPs at a concentration of 0.75 mg/mL, with interventions that included the copper chelator tetrathiomolybdate (TTM), NAC, and the MAPK inhibitor PD98059. Exposure to PS-NPs significantly increased cerebral copper accumulation (P < 0.05) and induced cuproptosis, characterized by lipid-acylated DLAT oligomerization, dysregulation of cuproptosis regulators (FDX1, LIAS, HSP70), and mitochondrial damage. In murine models, PS-NPs elicited neurotoxicity, as evidenced by neuronal loss, decreased Nissl body density, impaired synaptic plasticity, and suppressed oxidative stress markers (GSH, SOD, Nrf2), alongside activation of the ERK-MAPK pathway, ultimately resulting in deficits in learning and memory. Treatment with NAC alleviated these adverse effects. In SH-SY5Y cells, exposure to PS-NPs resulted in reduced cell viability (p < 0.01), an effect that was mitigated by TTM. Furthermore, NAC and PD98059 were found to reverse elevated copper levels, cuproptosis markers, and mitochondrial anomalies (p < 0.05). This study presents preliminary evidence indicating that PS-NPs may induce neuronal cuproptosis, potentially through the oxidative stress-mediated activation of the ERK-MAPK pathway, which contributes to cognitive dysfunction in mice. These findings provide insights into the potential mechanisms underlying PS-NPs neurotoxicity and highlight possible therapeutic targets, such as copper chelation or MAPK inhibition, for mitigating the neurological risks associated with nanoplastic exposure, pending further validation in human-relevant models.

Dementia is a serious public health problem. The more extensive dementia knowledge is, the more conducive it is to early prevention and treatment of dementia. However, no assessment of the general population’s dementia awareness has been conducted so far in China. Thus, this study assessed the national public knowledge of dementia based on mobile internet in China. We assessed 10,562 national respondents recruited based on the most popular social networking service in China, WeChat and analyzed the data using quantitative methods. The overall correct rate of total dementia knowledge was 63.14%. Only half of the participants (50.84%) could identify risk factors accurately. The level of dementia knowledge was positively associated with high education, city residency, and experience of exposure to information on dementia. The sandwich generation (aged 20–60 years) had the highest level of dementia knowledge. Chinese people were found to have a low level of knowledge about dementia, especially those aged over 60 years, with low education and living in rural areas. Further educational programs and campaigns are needed to improve dementia knowledge, with greater focus on the older population as the target audience, emphasis on dementia risk factors as educational content, correcting misconceptions about dementia, and providing more experience of exposure to dementia.

Neurodevelopmental disorders (NDDs) include various neurological disorders with high genetic heterogeneity, characterized by delayed or impaired cognition, communication, adaptive behavior, and psychomotor skills. These disorders result in significant morbidity for children, thus burdening families and healthcare/educational systems. However, there is a lack of early diagnosis and effective therapies. Therefore, a more connected approach is required to explore these disorders. Microglia, the primary phagocytic cells within the central nervous system, are crucial in regulating neuronal viability, influencing synaptic dynamics, and determining neurodevelopmental outcomes. Although the neurobiological basis of autism spectrum disorder (ASD) and schizophrenia (SZ) has attracted attention in recent decades, the role of microglia in ASD and SZ remains unclear and requires further discussion. In this review, the important and frequently multifaceted roles that microglia play during neurodevelopment are meticulously emphasized and potential microglial mechanisms that might be involved in conditions such as ASD and SZ are postulated. It is of utmost importance to acquire a comprehensive understanding of the complexities of the interplay between microglia and neurons to design effective, targeted therapeutic strategies to mitigate the effects of NDDs.

The hypothalamic–pituitary–adrenal axis regulates the secretion of glucocorticoids in response to environmental challenges. In the brain, a nuclear receptor transcription factor, the glucocorticoid receptor, is an important component of the hypothalamic–pituitary–adrenal axis’s negative feedback loop and plays a key role in regulating cognitive equilibrium and neuroplasticity. The glucocorticoid receptor influences cognitive processes, including glutamate neurotransmission, calcium signaling, and the activation of brain-derived neurotrophic factor–mediated pathways, through a combination of genomic and non-genomic mechanisms. Protein interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor, thereby affecting the hypothalamic–pituitary–adrenal axis and stress-related cognitive functions. An appropriate level of glucocorticoid receptor expression can improve cognitive function, while excessive glucocorticoid receptors or long-term exposure to glucocorticoids may lead to cognitive impairment. Patients with cognitive impairment–associated diseases, such as Alzheimer’s disease, aging, depression, Parkinson’s disease, Huntington’s disease, stroke, and addiction, often present with dysregulation of the hypothalamic–pituitary–adrenal axis and glucocorticoid receptor expression. This review provides a comprehensive overview of the functions of the glucocorticoid receptor in the hypothalamic–pituitary–adrenal axis and cognitive activities. It emphasizes that appropriate glucocorticoid receptor signaling facilitates learning and memory, while its dysregulation can lead to cognitive impairment. This provides clues about how glucocorticoid receptor signaling can be targeted to overcome cognitive disability-related disorders.